1. Field of the Invention
This invention relates to a series of aminoalkylsubstituted naphthalenediols or naphthols useful as cardiotonic and/or antimicrobial agents and to intermediates for the preparation thereof.
2. Prior Art
The compounds disclosed in the following references are believed to be the art most pertinent to the present invention. Bond et al., U.S. Pat. No. 3,463,808, patented Aug. 26, 1969 discloses a group of naphthalene derivatives of the formula ##STR1## wherein R.sup.1 stands for hydrogen or an alkyl, hydroxyalkyl, cycloalkyl, alkenyl or arylalkyl radical and ring B bears a hydroxy or acyloxy substituent or it bears two alkoxy substituents and wherein the naphthalene nucleus optionally bears one or more additional substituents and the esters thereof and the salts thereof. These compounds are stated to be .beta.-adrenergic blocking agents.
Webb, et al. U.S. Pat. No. 3,131,214, patented Apr. 28, 1964 discloses as insecticides a group of 3-dimethylaminomethyl-4-methyl-1,8-di-substituted naphthalenes of the formula ##STR2## wherein R is hydrogen, lower alkyl or lower acyl.
Sus U.S. Pat. No. 3,046,117, patented July 24, 1962 discloses in most pertinent part a group of 2(or 4)-hydroxy-1-naphthylmethylamines and 2,7-dihydroxy-1-naphthylmethylamines as intermediates in the preparation of light-sensitive orthoquinone diazides used in the manufacture of printing plates.
Stephenson U.S. Pat. No. 3,215,732, patented Nov. 2, 1965 which relates to a group of naphthalene derivatives stated to be of value in the treatment or prophylaxis of coronary artery disease discloses in most pertinent part [2-hydroxy-2-(6'-methoxy-2'-naphthyl)-ethyl]isopropylamine.
Horil et al., Chem. Pharm. Bull., 19, 1245-1256 (1971) discloses as chemical intermediates a group of mono- and dimethoxy-N,N-dimethylnaphthalenemethylamines.
Khorana, Indian J. Pharm., 23, 297 (1961); Chemical Abstracts, 57, 15023d (1962) discloses in most pertinent part 6-hydroxy-2-naphthaleneacetanilide.
S. V. Kessar, Tetrahedron Letters, 3245-3247 (1965) discloses as a chemical intermediate 6-methoxy-1-naphthylethylamine.
Beaudet, et al., Bull. Ste. Chim. Biol. 34, 952-955 (1952) discloses 7-methoxy-1-naphthylethylamine as a potential intermediate in the preparation of the corresponding 7-hydroxy-compound. However, preparation of the latter was unsuccessful.
Dey et al., Arch. Pharm., 277, 359-374 (1939) discloses in most pertinent part 2-methoxy and 2-hydroxy-1-naphthylmethylamine as chemical intermediates.
King et al., J. Chem. Soc., 1307-1315 (1940) discloses in most pertinent part 7-methoxy-.alpha.-piperidinomethyl-1-naphthalenemethanol which was tested and found inactive as an antiplasmodial agent.
Winstein et al., J. Org. Chem., 11, 150-156 (1946) discloses a method for the preparation of 4-methoxy-.alpha.-(dibutylaminomethyl)-1-naphthalenemethanol.
A. Madinaveitia, Anal. Fis. Quim., 18, 66 (1920); Chemical Abstracts 16, 92 (1922) discloses 1-aminoacetyl-4-methoxynaphthalene.
H. L. Holmes et al., JACS, 69, 2000-2003 (1947) discloses as a chemical intermediate 6,7-dimethoxy-2-naphthamide.
W. H. Hartung et al., JACS, 57, 1091-1093 (1935) discloses 2-oximino propionaphthone as a chemical intermediate.
Syntex Corporation, British Pat. No. 1,276,261, published June 1, 1972, discloses a group of substituted 2-(5',7'-dimethoxy-2'-naphthyl)propionamides stated to be useful as analgesic, anti-pyretic and anti-inflammatory agents.
3. Prior Publications
The following publications appeared subsequent to the invention claimed herein and less than one year prior to the filing date of parent application Ser. No. 388,962.
K. Y. Zee-Cheng et al., J. Heterocyclic Chem., 9, 805-811, (1972) discloses as chemical intermediates a group of naphthylethylamines having the formula ##STR3## wherein R.sub.1 .dbd.R.sub.2 .dbd.CH.sub.3 and R.dbd.H, CH.sub.3 or C.sub.6 H.sub.5 CH.sub.2
R.sub.1 +R.sub.2 =CH.sub.2 and R.dbd.H. PA1 Q is hydrogen or methyl; PA1 A is carbonyl, CHOH, a direct linkage or CR.sub.5 R.sub.6 where R.sub.5 and R.sub.6 are independently hydrogen or methyl; PA1 R.sub.2 is hydrogen or methyl, provided that when A is a direct linkage, or when R.sub.5 and/or R.sub.6 are methyl, then R.sub.2 is hydrogen; PA1 R.sub.3 and R.sub.4 are independently hydrogen, lower-alkyl, benzyl, aryl, or NR.sub.3 R.sub.4 is pyrrolidino, piperidino, hexamethyleneimino, morpholino or any of these having from one to two loweralkyl substituents; PA1 or an acid-addition salt thereof; PA1 provided that when A is CR.sub.5 R.sub.6 and R.sub.3 and R.sub.4 are independently hydrogen, lower-alkyl, benzyl or aryl, then at least one of R and R.sub.1 is lower-alkanoyl or aroyl. PA1 the side chain represented by ##STR7## occupies position 6 of the naphthalene nucleus; R, R.sub.1 and R.sub.2 are hydrogen; PA1 A is CR.sub.5 R.sub.6 where R.sub.5 and R.sub.6 are both hydrogen; and PA1 NR.sub.3 R.sub.4 is pyrrolidino, piperidino, hexamethyleneimino, morpholino or any of these having from one to two lower-alkyl substituents. PA1 Q is hydrogen or methyl; PA1 R.sub.2, R.sub.7 and R.sub.8 are independently hydrogen or methyl; PA1 Z is hydrogen, hydroxy or methoxy; and PA1 n is 1, 2 or 3; PA1 or an acid-addition salt thereof. PA1 R.sub.5 and R.sub.6 are independently hydrogen or methyl; and PA1 R.sub.3 and R.sub.4 are independently hydrogen, lower-alkyl, aryl, or NR.sub.3 R.sub.4 is pyrrolidino, piperidino, hexamethyleneimino, morpholino or any of these having from one to two lower-alkyl substituents; PA1 or an acid-addition salt thereof. PA1 A is carbonyl, CHOH or methylene; PA1 R.sub.2 is hydrogen or methyl, and PA1 R.sub.3 and R.sub.4 are independently hydrogen, lower-alkyl, benzyl, aryl, or NR.sub.3 R.sub.4 is pyrrolidino, piperidino, hexamethyleneimino, morpholino or any of these having from one to two loweralkyl substituents; PA1 or an acid-addition salt thereof. PA1 R.sub.2, R.sub.5 and R.sub.6 are each hydrogen or methyl provided that when R.sub.2 is methyl, R.sub.5 and R.sub.6 are hydrogen; PA1 R.sub.3 and R.sub.4 are hydrogen, lower-alkyl, benzyl, aryl or NR.sub.3 R.sub.4 is pyrrolidino, piperidino, hexamethyleneimino, morpholino or any of these having from one to two lower-alkyl substituents; PA1 or an acid-addition salt thereof. PA1 Q is hydrogen or methyl; PA1 A is carbonyl, a direct linkage or CR.sub.5 R.sub.6 where R.sub.5 and R.sub.6 are independently hydrogen or methyl; PA1 R.sub.2 is hydrogen or methyl, provided that when A is a direct linkage, or when R.sub.5 and/or R.sub.6 are methyl then R.sub.2 is hydrogen, and PA1 R.sub.3 and R.sub.4 are independently hydrogen, lower-alkyl, benzyl, aryl or NR.sub.3 R.sub.4 is pyrrolidino, piperidino, hexamethyleneimino, morpholino or any of these having from one to two loweralkyl substituents; provided that when A is carbonyl and R.sub.2 is hydrogen, then NR.sub.3 R.sub.4 is not amino, and when A is methylene and R.sub.2 is hydrogen, then NR.sub.3 R.sub.4 is not methylamino or benzylamino; PA1 or an acid-addition salt thereof. PA1 the side chain represented by ##STR17## occupies position 2 of the naphthalene nucleus; R is lower-alkyl; PA1 R.sub.2 is hydrogen; PA1 A is CR.sub.5 R.sub.6 where R.sub.5 and R.sub.6 are both hydrogen; PA1 R.sub.3, R.sub.4 and NR.sub.3 R.sub.4 have the same significance indicated hereinabove. PA1 Q is hydrogen or methyl; PA1 R.sub.2, R.sub.7 and R.sub.8 are independently hydrogen or methyl; PA1 Z is hydrogen, hydroxy or methoxy; and PA1 n is 1, 2 or 3; PA1 or an acid-addition salt thereof. PA1 R.sub.5 and R.sub.6 are independently hydrogen, or methyl; and PA1 R.sub.3 and R.sub.4 are independently hydrogen, lower-alkyl, benzyl, aryl or NR.sub.3 R.sub.4 is pyrrolidino, piperidino, hexamethyleneimino, morpholino or any of these having from one to two loweralkyl substituents; PA1 or an acid-addition salt thereof. PA1 A is carbonyl, CHOH or methylene; PA1 R.sub.2 is hydrogen or methyl, and PA1 R.sub.3 and R.sub.4 are independently hydrogen, lower-alkyl, benzyl, aryl or NR.sub.3 R.sub.4 is pyrrolidino, piperidino, hexamethyleneimino, morpholino or any of these having from one to two loweralkyl substituents; PA1 or an acid-addition salt thereof. PA1 R is lower-alkyl or benzyl; PA1 R.sub.2, R.sub.5 and R.sub.6 are each hydrogen or methyl, provided that when R.sub.2 is methyl R.sub.5 and R.sub.6 are hydrogen; PA1 R.sub.3 and R.sub.4 are independently hydrogen, lower-alkyl, benzyl, aryl or NR.sub.3 R.sub.4 is pyrrolidino, piperidino, hexamethyleneimino, morpholino or any of these having from one to two loweralkyl substituents; PA1 or an acid-addition salt thereof. PA1 R is lower-alkyl or benzyl; or both R groups together constitute a methylene group bonded to both oxygen atoms; PA1 X is chlorine or bromine; PA1 Q and R.sub.2 are independently hydrogen or methyl, and PA1 R.sub.3 and R.sub.4 are independently hydrogen, lower-alkyl, benzyl, aryl or NR.sub.3 R.sub.4 is pyrrolidino, piperidino, hexamethyleneimino, morpholino or any of these having from one to two lower-alkyl substituents; PA1 or an acid-addition salt thereof. PA1 R is lower-alkyl or benzyl; or both R groups together constitute a methylene group bonded to both oxygen atoms; PA1 Q is hydrogen or methyl, and PA1 R.sub.3 and R.sub.4 are independently hydrogen, lower-alkyl, benzyl, aryl or NR.sub.3 R.sub.4 is pyrrolidino, piperidino, hexamethyleneimino, morpholino or any of these having from one to two lower-alkyl substituents. PA1 R is lower-alkyl or benzyl; or both R groups together constitute a methylene group bonded to both oxygen atoms; PA1 Q and R.sub.2 are independently hydrogen or methyl; and PA1 X is chlorine, bromine or iodine. PA1 R is lower-alkyl or benzyl; or both R groups together constitute a methylene group bonded to both oxygen atoms; PA1 Q is hydrogen or methyl; and PA1 X is chlorine, bromine or p-toluenesulfonate. PA1 Q, R.sub.5 and R.sub.6 are independently hydrogen or methyl. PA1 Q is hydrogen or methyl; PA1 R is lower-alkyl or benzyl; or both R groups together constitute a methylene group bonded to both oxygen atoms; PA1 R.sub.3 and R.sub.4 are independently hydrogen, lower-alkyl, benzyl, aryl or NR.sub.3 R.sub.4 is pyrrolidino, piperidino, hexamethyleneimino, morpholino or any of these having from one to two lower-alkyl substituents, provided that when the side chain --CONR.sub.3 R.sub.4 occupies position 2, R.sub.3 and R.sub.4 are not both hydrogen. PA1 R.sub.5 and R.sub.6 are independently hydrogen or methyl. PA1 R.sub.2 is hydrogen or methyl and PA1 X is chlorine, bromine or iodine. PA1 R is lower-alkyl or benzyl; PA1 R.sub.5 is hydrogen or methyl, and PA1 R.sub.3 and R.sub.4 are independently hydrogen, lower-alkyl, benzyl, aryl or NR.sub.3 R.sub.4 is pyrrolidino, piperidino, hexamethyleneimino, morpholino or any of these having from one to two lower-alkyl substituents. PA1 R is lower-alkyl or benzyl, and PA1 R.sub.5 and R.sub.6 are independently hydrogen or methyl. PA1 A is carbonyl or CHOH; PA1 R is lower-alkyl or benzyl; PA1 R.sub.3 and R.sub.4 are independently hydrogen, lower-alkyl, benzyl, aryl or NR.sub.3 R.sub.4 is pyrrolidino, piperidino, hexamethyleneimino, morpholino or any of these having from one to two lower-alkyl substituents. PA1 Q is hydrogen or methyl. PA1 R is lower-alkyl or benzyl; or both R groups together constitute a methylene group bonded to both oxygen atoms; PA1 Q is hydrogen or methyl, and PA1 X is chlorine or bromine. PA1 R is lower-alkyl or benzyl; or both R groups together constitute a methylene group bonded to both oxygen atoms, and PA1 Q is hydrogen or methyl. PA1 R is lower-alkyl or benzyl; or both R groups together constitute a methylene group bonded to both oxygen atoms, and PA1 Q is hydrogen or methyl. PA1 X is chlorine or bromine; PA1 R is lower-alkyl or benzyl; or both R groups together constitute a methylene group bonded to both oxygen atoms, and PA1 Q is hydrogen or methyl. PA1 R is lower-alkyl or benzyl. PA1 Q is hydrogen or methyl, and PA1 A is carbonyl or CHOH. PA1 R is hydrogen, lower-alkyl or benzyl; or both R groups together constitute a methylene group bonded to both oxygen atoms, and PA1 Q is hydrogen or methyl. PA1 R is lower-alkyl or benzyl; or both R groups together constitute a methylene group bonded to both oxygen atoms, and PA1 Q is hydrogen or methyl. PA1 Q is hydrogen or methyl. PA1 R is lower-alkyl or benzyl; or both R groups together constitute a methylene group bonded to both oxygen atoms, and PA1 Q is hydrogen or methyl provided that when the carboxyl group occupies position 2, Q is methyl. PA1 Q and R.sub.2 are independently hydrogen or methyl, and PA1 the side chain represented by --COCH.sub.2 R.sub.2 occupies either position 1 or position 2 of the naphthalene nucleus, provided that when said side chain occupies position 2, Q is methyl. PA1 A is carbonyl or CHOH. PA1 R.sub.2 is hydrogen or methyl. PA1 Q is hydrogen or methyl; PA1 R is lower-alkyl or benzyl; and PA1 X is chlorine, bromine or iodine using the procedure described hereinabove for the preparation of the amino ketones of Formula VI (A is C.dbd.O) from the corresponding halo ketones (Formula XIII).
Richardson-Merrell, Belgian Pat. No. 783,271, published Sept. 1, 1972, discloses as intermediates compounds having the formula ##STR4## wherein inter alia Y is 1 to 6 carbon alkylene and R is 1 to 3 carbon alkoxy. However, the only disclosure in the reference relating to alkoxy-substituted compounds resides in reference to the previously known 4-methoxy-.alpha.-methylnaphthalenemethylamine and 6-methoxy-1-naphthylethylamine described by Dey et al. and Kessar et al., both cited hereinabove.